- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00610051
ALP-1 Continuous Intravenous Infusion to Maintain Clinical Stability in Advanced Heart Failure
Phase 3 Study of Alprostadil Continuous Intravenous Infusion to Maintain Clinical Stability in Severe Heart Failure Patients
Study Overview
Detailed Description
This multicenter, double-blind, placebo-controlled, randomized, parallel-group trial will study up to approximately 700 patients with advanced HFrEF who are not expected to receive heart transplant or LVAD placement for 6 months after enrollment. Eligible patients will be randomized (1:1) to receive either alprostadil 250 μg/day, regardless of body weight, or placebo (normal saline) given in a continuous infusion. The treatments are further described in the section on Dose/Route/Regimen. Study drug administration will continue until study closure so long as clinically tolerated and the mortality endpoint has not been achieved; patients are to be followed for survival regardless of whether or not they remain on study drug. The difference in mortality rates between the two groups will be compared after approximately 350 deaths, LVAD placements, or heart transplantations have occurred. The study will include an embedded pilot evaluation of secondary nonfatal clinical endpoints and AESIs/ tolerability for purposes of possible protocol modification. Specifically, selected data for the first 70 patients entered (i.e., randomized) will be evaluated in an unblinded manner after the 6-month assessment of the last surviving patient (of the first 70 randomized patients) to discern the effects on (1) patient global assessment, KCCQ, and worsening heart failure events; (2) the occurrence of hypotension, joint/bone pain, diarrhea and headache; and (3) difficulties with protocol implementation. The interim assessment and possible revision of the primary endpoint are discussed further below in the roles of the independent review committees and in the Study Power and Planned Sample Size section.
The screening activities will be performed on stable patients on an outpatient basis or on recently hospitalized patients (inpatient) who are otherwise ready for discharge after clinical stabilization and stabilization of dose of diuretics. Selected patients need to be on all appropriate doses of recommended HF therapy as judged by the Investigator. Screening should not exceed 14 days. The following independent committees will be established and operate under charters outlining operational procedures and responsibilities, briefing desccribed as follows:
- A Steering Committee (SC), involved in initial protocol development, will review selected data from the embedded pilot phase; all-cause mortality data will not be shared. Following the placement of the central catheter in the first 70 patients, a determination will be made whether or not the subsequent entered patients need to be hospitalized for the first 24 hours; this assessment will be on the basis of blinded data accrued until discharge and the initial study nurse home visit. Once the last of the first 70 patients achieves the 6-month milestone, unblinded data, other than mortality, will be reviewed. If the analysis indicates that there is little unblinding based on tolerability (i.e., AESIs) and there is a reasonable expectation of clinical benefit on one or more of the secondary endpoints, the SC may designate one as primary or design and implement a "hierarchical composite" of the nonfatal and fatal events as the primary endpoint to be applied to all patients randomized into the trial AFTER the 70th randomized patient. If this were to occur, all-cause mortality would become a key secondary endpoint, to be analyzed for non-inferiority based on all randomized patients inclusive of the first 70 patients.
- A Data Safety Monitoring Board (DSMB) will review unblinded mortality and safety data at regular intervals throughout the study. The role of the DSMB will primarily be to advise the Sponsor on whether or not the study should continue.
Study Type
Enrollment (Anticipated)
Phase
- Phase 3
Contacts and Locations
Study Contact
- Name: Pei K Wang, MD
- Phone Number: +886227720395
- Email: pei@biopeutics.com
Study Contact Backup
- Name: Emily Tai, MA
- Phone Number: +886227720395
- Email: emilytai@biopeutics.com
Study Locations
-
-
-
Vienna, Austria
- Medical University Vienna
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
- Patients older than 18 years of age, of any gender/sex and race/ethnicity
Patients with a diagnosis of advanced HFrEF as evidenced by (all must apply):
- Left ventricular ejection fraction (LVEF) ≤30% by any acceptable method at the time of screening or documented within the previous 3 months
- Nt-proBNP >3000pg/mL or BNP >600pg/mL at screening
- New York Heart Association (NYHA) functional class IIIb or IV, i.e., chronic dyspnea or fatigue at rest or with minimal exertion at the time of screening or within the previous 3 months
- Renal dysfunction reflected by a glomerular filtration rate (GFR) <60 mL/min approximated by the Modification of Diet in Renal Disease formula.
- A clinical summary scoreof KCCQ of <50
- Patients on all appropriate recommended HF therapy.
- Patient should not be receiving continuous or planned intermittent intravenous infusions with a positive inotropic or vasodilator drug in a non-hospitalized setting
- Patients should not be considered as candidates for heart transplantation or LVAD for at least 6 months from randomization according to the opinion of the treating physician.
Women of childbearing potential (i.e., who have not undergone a hysterectomy or who have not been postmenopausal for at least 24 consecutive months) must commit either to abstain continuously from heterosexual sexual contact or to use at least one "highly effective" method of birth control (e.g., intrauterine device [IUD], hormonal contraception, tubal ligation, or partner's vasectomy) or two "effective" methods (e.g., latex condom, diaphragm, or cervical cap), beginning 4 weeks prior to screening and throughout study participation.
Note: As alprostadil is not genotoxic and female sexual partners of male study participants are not likely to have substantial exposure via semen, there are no contraception requirements for men.
- Patients must be willing and able to give written informed consent, including local data privacy consents, as required
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: trial arm
6 months central continuous infusion with Alp_1 by infusion pump.
|
central venous access continuous delivery with 500mcg/48 hours in active arm
|
Placebo Comparator: Placebo arm
6 months central infusion with NS by infusion pump with exact infusion rat as trial arm.
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central venous access continuous delivery with 500mcg/48 hours in active arm
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to all-cause mortality (defined as death, heart transplant, or LVAD placement)
Time Frame: 6 months infusion
|
To access the effect of continue long term ALP-1infusion at a fixed dose of at 500mcg/48 hr. in patinets with advanced heart failure with reduced ejection fraction(HrEF) compare to placebo.
|
6 months infusion
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
To assess the effect of continuous long-term alprostadil infusion compared to placebo on secondary efficacy endpoints over 6 months ALP-1-infusion over 52 weeks compared to placebo in patients with advanced HFrEF
Time Frame: 6 months
|
Patient Global Assessment
|
6 months
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Martin Huelsmann, MD, Medical University Vienna, department of Cardiology
- Principal Investigator: Noemi Pavo, MD PhD, Medical University Vienna, department of Cardiology
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 3-T02-07-0105
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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